The ultimate goal of this project is to understand the binding of drugs to nucleic acids in order to provide a foundation for the rational design of new drugs. The new method of fluorescence detected circular dichroism (FDCD) will be used to compare drug binding under various conditions. FDCD measures the difference in fluorescence intensity excited by left and right circularly polarized light. It provides a sensitive probe for conformation around a fluorescent drug. Since fluorescence has high detection sensitivity and specificity, it can be used to study drugs at low concentrations in complex systems. Drug binding in simple and complex systems will be compared. For example, is drug binding in vivo similar to drug binding to free DNA in solution? The effects of drug combinations on binding will also be considered.